Ophthalmic Antibiotic-Steroid Combinations Therapeutic Class Review (TCR)
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Ophthalmic Antibiotic–Steroid Combinations
Therapeutic Class Review (TCR)
March 23, 2021
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Attention: Legal Department
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The materials contained herein represent the opinions of the collective authors and editors and should
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This material is not intended to be relied upon as medical advice for specific medical cases and nothing
contained herein should be relied upon by any patient, medical professional or layperson seeking
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March 2021
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© 2004-2021 Magellan Rx Management. All Rights Reserved.FDA-APPROVED INDICATIONS
All the listed drugs are indicated for corticosteroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and
where bacterial infection or a risk of bacterial infection exists.
Drug Strength Manufacturer
dexamethasone / neomycin sulfate / polymyxin B sulfate 0.1%; EQ 3.5 mg base/mL; 10,000 units/mL generic, Alcon/Novartis
(Maxitrol) 1 (suspension, ointment)
dexamethasone / tobramycin 0.1%; 0.3% generic (suspension),
(TobraDex) 2,3 Alcon/Novartis (suspension),
Alcon/Novartis (ointment)
dexamethasone / tobramycin 0.05%; 0.3% Alcon/Eyevance (suspension)
(TobraDex ST) 4
hydrocortisone / neomycin sulfate / polymyxin B sulfate 5 1%; EQ 3.5 mg base/mL; 10,000 units/mL Sandoz (suspension)
hydrocortisone / neomycin sulfate / bacitracin zinc / polymyxin B sulfates 6
1%; EQ 3.5 mg base/gm; 400 units/gm; 10,000 units/gm generic (ointment)
loteprednol / tobramycin 0.5%; 0.3% Valeant/Bausch (suspension)
(Zylet®) 7
prednisolone acetate / gentamicin sulfate 1%; EQ 0.3% base Allergan (suspension)
(Pred-G) 8
prednisolone acetate / gentamicin sulfate 0.6%; EQ 0.3% base Allergan (ointment)
(Pred-G S.O.P.) 9
prednisolone acetate / sulfacetamide sodium 0.2%; 10% Allergan (suspension, ointment)
(Blephamide, Blephamide S.O.P.) 10
prednisolone sodium phosphate / sulfacetamide sodium 11 EQ 0.23% phosphate; 10% Valeant/Bausch
Ophthalmic Antibiotic–Steroid Combinations Review – March 2021
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© 2004-2021 Magellan Rx Management. All Rights Reserved.OVERVIEW 12
Infections of the eye can rapidly damage important functional structures and lead to permanent vision
loss or blindness. A corticosteroid will reduce inflammation and, when combined with an antibiotic, the
antibiotic treats or prevents an infection, which may be associated with the inflammation. The agents
within this class are indicated for corticosteroid-responsive inflammatory ocular conditions (e.g.,
bacterial conjunctivitis, corneal abrasion, uveitis) for which a corticosteroid is indicated and where
bacterial infection or a risk of bacterial infection exists.
PHARMACOLOGY 13
Corticosteroids provide local anti-inflammatory activity. Dexamethasone, hydrocortisone, loteprednol,
and prednisolone provide local anti-inflammatory activity. Loteprednol is an analog of prednisolone
and induces slightly less elevation of intraocular pressure (IOP) compared to prednisolone.
Antibiotics provide local antibacterial activity in the respective spectrums. Selection of the antibiotic
should depend on the known or suspected organisms involved in the potential or present infection.
Aminoglycosides, which include gentamicin, neomycin, and tobramycin, inhibit protein synthesis by
binding to the 30S ribosomal subunit.
Polymyxin B is bactericidal for a variety of gram-negative organisms. It increases the permeability of
the bacterial cell membrane by interacting with the phospholipid components of the membrane.
Bacitracin, which is bactericidal, inhibits bacterial growth through prevention of the addition of cell
wall subunits to the peptidoglycan chain.
Sulfacetamide is a synthetic sulfonamide that inhibits bacterial dihydrofolate synthetase, a bacterial
enzyme responsible for the conversion of p-aminobenzoic acid (PABA) into folic acid. Production of
folic acid is an essential component of bacterial development.
PHARMACOKINETICS 14
Ophthalmic ointments have the longest contact time between the drug and the ocular tissues;
however, ointments can impede delivery of other ophthalmic drugs by serving as a barrier. Ointments
are useful in children to decrease the loss of drug by tears. Compared to solutions, ophthalmic
suspensions mix with tears less rapidly and remain in the cul-de-sac longer. Systemic absorption of
these products is minimal.
CONTRAINDICATIONS/WARNINGS15,16,17,18,19,20,21,22,23
These combination agents are contraindicated in most viral diseases of the cornea and conjunctiva,
mycobacterial infection of the eye, and fungal diseases of ocular structures.
Prolonged use of corticosteroids may result in glaucoma, as well as increase the hazard of secondary
ocular infections. Corticosteroids should be used with caution in the presence of glaucoma. If
corticosteroid-containing ophthalmic preparations are used for 10 days or longer, IOP should be
monitored even though it may be difficult in children and uncooperative patients.
Neomycin has been associated with hypersensitivity reactions and cross-sensitization to other
aminoglycosides can occur. Dexamethasone/tobramycin (TobraDex) also carries the potential for
Ophthalmic Antibiotic–Steroid Combinations Review – March 2021
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© 2004-2021 Magellan Rx Management. All Rights Reserved.sensitivity with the severity of hypersensitivity reaction varying from localized to generalized (e.g.,
erythema, itching, urticaria, skin rash, anaphylaxis, anaphylactoid reactions, or bullous reactions).
DRUG INTERACTIONS
Based on the minimal extent of absorption with these agents, interactions with systemically
administered drugs are unlikely to occur.
ADVERSE EFFECTS 24,25,26,27,28,29,30,31,32,33,34
Most effects are related to local irritation on instillation. Occasionally, allergic sensitization (e.g.,
itching, swelling, and conjunctival erythema) may occur. Serious hypersensitivity reactions (e.g.,
anaphylaxis) are rare.
Corticosteroids have been associated with elevated IOP with possible development of glaucoma,
infrequent optic nerve damage, posterior subcapsular cataract formation, and delayed wound healing.
Studies in healthy volunteers showed loteprednol/tobramycin (Zylet) to cause less increase in IOP and
better tolerability compared to dexamethasone/tobramycin (TobraDex). Elevations in intraocular
pressure should not be clinically significant with short-term use.
Ulcerative keratitis, headache, and Stevens-Johnson syndrome have been reported with
neomycin/polymyxin B/dexamethasone (Maxitrol) post-marketing, and anaphylactic reaction,
erythema multiforme, has been reported in the post-marketing setting with
dexamethasone/tobramycin.
Secondary fungal and viral infections have been reported.
Adverse effects data are compiled from package inserts and cannot be considered comparative or all
inclusive.
SPECIAL POPULATIONS 35,36,37,38,39,40,41,42,43,44
Pediatrics
Safety and effectiveness of these agents in pediatrics have not been established, apart from
tobramycin/dexamethasone (TobraDex, TobraDex ST) and neomycin/polymyxin B/dexamethasone
(Maxitrol), which are indicated in patients 2 years and older. Data are available for patients older than
2 months for prednisolone/sulfacetamide (Blephamide).
In clinical trials, loteprednol/tobramycin (Zylet) did not show efficacy for lid inflammation or
blepharoconjunctivitis in pediatric patients aged 0 to 6 years.
Pregnancy
Neomycin/polymyxin B/dexamethasone (Maxitrol), dexamethasone/tobramycin (TobraDex), and
prednisolone acetate/gentamicin sulfate (Pred-G) were previously Pregnancy Category C agents, but
the drug labeling has been updated to comply with the Pregnancy and Lactation Labeling Rule (PLLR).
The current labeling state that there are no adequate studies in pregnant women;
neomycin/polymyxin B/dexamethasone and dexamethasone/tobramycin labeling also states that
prolonged or repeated use of a corticosteroid during pregnancy has been associated with intra-uterine
growth retardation. The remaining products in this class are Pregnancy Category C.
Ophthalmic Antibiotic–Steroid Combinations Review – March 2021
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© 2004-2021 Magellan Rx Management. All Rights Reserved.DOSAGES 45,46,47,48,49
Apply to affected eye(s).
Drug Ointment Dosage Dropper Dosage Availability
0.1% dexamethasone / 0.35% neomycin base / Apply every 3 to 4 1 to 2 drops every 3 to 5 mL suspension;
10,000 units polymyxin B sulfate (Maxitrol) hours 4 hours 3.5 g ointment
0.1% dexamethasone / 0.3% tobramycin 1 to 2 drops every 4 to
(TobraDex) 6 hours; During the
2.5 mL, 5 mL, and
½ inch up to 3 or 4 first 24 to 48 hours, the
10 mL suspension;
times daily dosage may be
3.5 g ointment
increased to 1 to 2
drops every 2 hours
0.05% dexamethasone / 0.3% tobramycin 1 drop every 4 to 6
(TobraDex ST) hours; During the initial
-- 24 to 48 hours, dosage 5 mL suspension
may be increased to 1
drop every 2 hours
1% hydrocortisone / 0.35% neomycin sulfate / 1 to 2 drops every 3 to
-- 7.5 mL suspension
10,000 units polymyxin B suspension 4 hours
1% hydrocortisone / 0.35% neomycin base / 400
Apply every 3 to 4
units bacitracin zinc / 10,000 units polymyxin B -- 3.5 g ointment
hours
ointment
0.5% loteprednol / 0.3% tobramycin suspension 1 to 2 drops every 4 to
(Zylet) 6 hours; during the first
5 mL and 10 mL
-- 24 to 48 hours, may
suspension
increase to 1 to 2 drops
every 2 hours
1% prednisolone / 0.3% gentamicin base 1 drop 2 to 4 times
suspension (Pred-G) ½ inch 1 to 3 times daily; May increase to 1 5 mL suspension;
0.6% prednisolone / 0.3% gentamicin base daily drop every hour during 3.5 g ointment
ointment (Pred-G S.O.P.) first 24 to 48 hours
0.2% prednisolone / 10% sulfacetamide
5 mL and 10 mL
suspension (Blephamide) ½ inch up to 3 or 4 1 to 3 drops every 1 to
suspension;
0.2% prednisolone / 10% sulfacetamide ointment times daily 4 hours
3.5 g ointment
(Blephamide S.O.P.)
0.23% prednisolone / 10% sulfacetamide solution 1 to 3 drops every 1 to
-- 5 mL solution
4 hours
Ophthalmic Antibiotic–Steroid Combinations Review – March 2021
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© 2004-2021 Magellan Rx Management. All Rights Reserved.CLINICAL TRIALS
Search Strategy
Articles were identified through searches performed on PubMed and review of information sent by
manufacturers. Search strategy included the FDA-approved use of all drugs in this class. Studies
included for analysis in the review were published in English, performed with human participants, and
randomly allocated participants to comparison groups. In addition, studies must contain clearly stated,
predetermined outcome measure(s) of known or probable clinical importance, use data analysis
techniques consistent with the study question, and include follow-up (endpoint assessment) of at least
80% of participants entering the investigation. Despite some inherent bias found in all studies,
including those sponsored and/or funded by pharmaceutical manufacturers, the studies in this
therapeutic class review were determined to have results or conclusions that do not suggest
systematic error in their experimental study design. While the potential influence of manufacturer
sponsorship and/or funding must be considered, the studies in this review have also been evaluated
for validity and importance.
Very little good quality comparative data have been published for the products in this class.
tobramycin/dexamethasone (TobraDex) and tobramycin/loteprednol (Zylet)
In a double-blind, randomized trial, tobramycin/dexamethasone and tobramycin/loteprednol were
compared for effectiveness in controlling inflammation in 40 patients with blepharo-
keratoconjunctivitis. 50 Patients received tobramycin 0.3%/dexamethasone 0.1% or tobramycin
0.3%/loteprednol 0.5% twice daily in the test eye. Baseline evaluation recorded the severity of
blepharitis, conjunctivitis, ocular discharge, and corneal punctuate epithelial keratopathy on a scale of
3 (extensive) to 0 (minimum) for each component. Patients with a total score of greater than 6 were
included in the trial. After 3 to 5 days, the ocular surface was re-evaluated for treatment response. No
significant differences were noted between the groups at baseline. Mean post-treatment scores were
as follows: total ocular surface scores, 1.8 and 3.4 (p=0.002); blepharitis scores, 0.9 and 1.35 (p=0.017);
discharge scores, 0.2 and 0.6 (p=0.025); and conjunctivitis scores, 0.15 and 0.6 (p=0.013) for
tobramycin/dexamethasone and tobramycin/loteprednol, respectively. Corneal punctuate epithelial
keratopathy scores were similar in both groups. Tobramycin 0.3%/dexamethasone 0.1% significantly
decreased clinical signs of ocular inflammation and total ocular inflammation scores when compared
with tobramycin 0.3%/loteprednol 0.5% in patients with moderate to severe
blepharokeratoconjunctivitis.
SUMMARY
A wide variety of combinations of corticosteroids and antibiotics are available in this class. Several
agents are available as ointments and suspensions. There are not enough published comparative trials
to distinguish any of the available products from the others.
Ophthalmic Antibiotic–Steroid Combinations Review – March 2021
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© 2004-2021 Magellan Rx Management. All Rights Reserved.REFERENCES
1 Maxitrol [package insert]. Fort Worth, TX; Alcon; May 2018.
2 TobraDex suspension [package insert]. Fort Worth, TX; Alcon; April 2020.
3 TobraDex ointment [package insert]. Fort Worth, TX; Alcon. April 2020.
4 TobraDex ST [package insert]. Fort Worth, TX; Alcon; February 2009.
5 Available at: http://clinicalpharmacology.com. Accessed March24, 2021.
6 Available at: http://clinicalpharmacology.com. Accessed March 24, 2021.
7 Zylet [package insert]. Tampa, FL; Bausch and Lomb; September 2019.
8 Pred-G [package insert]. Irvine, CA; Allergan; July 2018.
9 Available at: http://clinicalpharmacology.com. Accessed March 24, 2021.
10 Available at: http://clinicalpharmacology.com. Accessed March 24, 2021.
11 Available at: http://clinicalpharmacology.com. Accessed March 24, 2021.
12 Available at: http://clinicalpharmacology.com. Accessed March 24, 2021.
13 Available at: http://clinicalpharmacology.com. Accessed March 24, 2021.
14 Available at: http://clinicalpharmacology.com. Accessed March 24, 2021.
15 Cortisporin ointment [package insert]. Bristol, TN; Monarch; August 2003.
16 Cortisporin suspension [package insert]. Bristol, TN; Monarch; July 2003.
17 TobraDex ointment [package insert]. Fort Worth, TX; Alcon; April 2020.
18 TobraDex suspension [package insert]. Fort Worth, TX; Alcon; April 2020.
19 Zylet [package insert]. Tampa, FL; Bausch and Lomb; September 2019.
20 Maxitrol [package insert]. Fort Worth, TX; Alcon; May 2018.
21 Pred-G [package insert]. Irvine, CA; Allergan; July 2018.
22 Available at: http://clinicalpharmacology.com. Accessed March 24, 2021.
23 TobraDex ST [package insert]. Fort Worth, TX; Alcon; February 2009.
24 Cortisporin ointment [package insert]. Bristol, TN; Monarch; August 2003.
25 Cortisporin suspension [package insert]. Bristol, TN; Monarch; July 2003.
26 TobraDex ointment [package insert]. Fort Worth, TX; Alcon; April 2020.
27 TobraDex suspension [package insert]. Fort Worth, TX; Alcon; April 2020.
28 Zylet [package insert]. Tampa, FL; Bausch and Lomb; September 2019.
29 Maxitrol [package insert]. Fort Worth, TX; Alcon; May 2018.
30 Pred-G [package insert]. Irvine, CA; Allergan; July 2018.
31 Available at: http://clinicalpharmacology.com. Accessed March 24, 2021.
32 TobraDex ST [package insert]. Fort Worth, TX; Alcon; February 2009.
33 Holland EJ, Bartlett JD, Paterno MR, et al. Effects of loteprednol/tobramycin versus dexamethasone/tobramycin on intraocular pressure in healthy
volunteers. Cornea. 2008; 27(1): 50-55.
34 Bartlett JD, Holland EJ, Usner DW, et al. Tolerability of loteprednol/tobramycin versus dexamethasone/tobramycin in healthy volunteers: results of a 4-
week, randomized, double-masked, parallel-group study. Curr Med Res Opin. 2008; 24(8): 2,219-2,227.
35 Cortisporin ointment [package insert]. Bristol, TN; Monarch; August 2003.
36 Cortisporin suspension [package insert]. Bristol, TN; Monarch; July 2003.
37 TobraDex ointment [package insert]. Fort Worth, TX; Alcon; April 2020.
38 TobraDex suspension [package insert]. Fort Worth, TX; Alcon; April 2020.
39 Zylet [package insert]. Tampa, FL; Bausch and Lomb; September 2019.
40 Maxitrol [package insert]. Fort Worth, TX; Alcon; May 2018
41 Pred-G [package insert]. Irvine, CA; Allergan; July 2018.
42 Available at: http://clinicalpharmacology.com. Accessed March 24, 2021
43 TobraDex ST [package insert]. Fort Worth, TX; Alcon; February 2009.
44 Zylet [package insert]. Tampa, FL; Bausch and Lomb; September 2019.
45 Available at: http://clinicalpharmacology.com. Accessed March 24, 2021
46 TobraDex suspension [package insert]. Fort Worth, TX; Alcon; April 2020.
47 Zylet [package insert]. Tampa, FL; Bausch and Lomb; September 2019.
48 Pred-G [package insert]. Irvine, CA; Allergan; July 2018.
49 TobraDex ST [package insert]. Fort Worth, TX; Alcon; February 2009.
50 Rhee SS. Mah FS. Comparison of tobramycin 0.3%/dexamethasone 0.1% and tobramycin 0.3%/loteprednol 0.5% in the management of blepharo-
keratoconjunctivitis. Adv Ther. 2007; 24(1): 60-67.
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